Leukemia is a malignant neoplasm (cancer) of the white blood cells, the cells that make up our defense system against invading germs. There are 4 major types of leukemia, known as acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL).
White blood cells, or leukocytes, are cells produced in the bone marrow and are present in the blood, lymphatic system (lymph and lymph), and organs such as liver and spleen. These cells have as basic function the defense of the organism against invaders, either attacking them directly or producing antibodies against specific invaders.
Every day millions of leukocytes are created and destroyed in our body. The bone marrow produces on average 100 million leukocytes per day. On average, we have a concentration of 4,000 to 11,000 cells in every milliliter of blood in our body.
When an infection occurs, the body begins to produce more leukocytes to increase our defenses, returning to normal levels after the resolution of the picture. In cases of infection, the blood leukocyte concentration generally increases up to 20,000 cells per milliliter.
Leukemia is characterized by the excessive and inappropriate production of defective leukocytes, often exceeding by far the normal or expected blood values for cases of infection. Some leukemia may present with more than 100,000 leukocytes / ml.
There are 5 different types of leukocytes:
Neutrophils
Eosinophils
Basophils
Lymphocytes
Monocytes
Read this part carefully. If you understand it, you are ready to know all about leukemia.
Inside our bone marrow there are stem cells, called stem cells or precursor cells, which will give rise to all cells circulating in the blood, namely leukocytes, white blood cells, platelets and red blood cells.
The stem cell divides first into two groups: myeloid cells and lymphoid cells.
Myelogenous primordial cells will develop and give rise to:
Leukocytes of the neutrophil line, eosinophils, basophils and monocytes
Blood cells or red blood cells
Platelets
The primordial lymphoid cells will give rise to:
Leukocytes of the lymphocyte lineage (B lymphocytes and T lymphocytes)
Each of the strains described above can turn into cancer, which justifies the existence of different types of leukemia.
Although leukemia is primarily a disease of leukocytes, it is possible to have leukemias of the myeloid series affecting platelets or red blood cells.
Based on the above, we can understand why leukemias are divided into myeloid leukemias (also called myeloblastic or myelocytic leukemias) and lymphocytic leukemias (also called lymphoblastic or lymphocytic leukemias), according to the lineage that undergoes malignant transformation.
The second classification is between acute leukemias and chronic leukemias. The acute ones are those caused by the excessive production of young leucocytes, called blasts, whereas the chronic one occurs by accumulation of mature leukocytes. In both forms, both mature leukocytes and blasts are defective cells, lacking function, and produced uncontrollably.
Well, we reached the final classification of the main leukemias. Are they:
Acute myeloid leukemia (AML)
Chronic myeloid leukemia (CML)
Acute lymphocytic leukemia (ALL)
Chronic lymphocytic leukemia (CLL)
Before we talk a little bit about each of the 4 main types of leukemia, we will describe the main symptoms of the disease.
Regardless of the type of leukemia that a patient may have, there is a range of signs and symptoms that are common to the 4 large groups.
Cancerous leukocytes are born and proliferate initially in the bone marrow. With that, we ended up having the marrow occupied by an immense amount of just one clone of defective cells, preventing the production of all other blood cell lines.
The end result is that the marrow can no longer produce red blood cells properly, leading to anemia; can no longer produce platelets, facilitating the occurrence of bleeding; and can no longer produce the other types of leukocytes, leaving the body unprotected against infections.
The leukemic cells are not restricted to the bone marrow, spreading through the blood and invading tissues and organs like any other cancer.
The diagnosis of leukemia is suggested by the set of signs and symptoms associated with a large increase in leukocyte counts in the blood count (leukemia can be present without leukocyte changes in the blood count). However, the confirmation of the existence of leukemia is through bone marrow biopsy.
Although they are all grouped in the leukemias group, each one has a different clinical picture, treatment and prognosis. Let's then look at the 4 main types of leukemia in more detail.
AML occurs by malignant transformation of the young cells (blasts) that will give rise to myeloid blood line (part of the leukocytes, red blood cells and platelets).
It can occur in all ages, sex and ethnicity, but it is more common in adults over 60, males and whites. Previous exposure to chemotherapy, radiation or toxic products, such as benzene, appears to increase the risk. The cigarette, has numerous toxic substances, among them benzene itself, favoring the appearance of leukemias.
The LMA is divided into subgroups. The oldest classification is done in 7 subgroups (M1 to M7) according to the type of neoplastic cell (platelets, monocytes, neutrophils, eosinophils, erythrocytes, etc.). The most current classification is even more complex and involves, besides the type of cell involved, the mutation in the chromosome responsible for the malignancy.
Treatment of AML
LMA is still a disease with a low cure rate. The response to treatment depends on several factors including the type of chromosomal mutation responsible for the neoplasm, age (better in young, worse in the elderly) and the state of health of the patient.
The treatment is done with chemotherapy, being divided in two phases: Induction and consolidation.
The induction is the attempt to eliminate all cancer cells and usually lasts 4 weeks.
Once all cancer cells are eliminated, the consolidation phase aims to prevent the marrow from continuing to produce new malignant cells. The consolidation phase can be done with new cycles of chemotherapy or with bone marrow transplantation.
Currently about 30% of adults under 60 reach cure criteria (more than 5 years free of disease). Among patients over 60, this rate falls below 10%.
CML is the malignant transformation of adult cells of the myeloid series. It is a disease with a more tragic course than the acute form. However, after 5 years there is a risk of blastic transformation, that is, of exacerbation, becoming as aggressive as AML.
CML is caused by a defect in a chromosome, which becomes shorter than usual, called the Philadelphia chromosome. This defect is not transmitted from the parents to the children, but acquired during the life. There are already tests that detect the presence of this defective chromosome.
Unlike LMA, CML practically only affects adults between 30 and 50 years, being very rare in children and young people. When it occurs under the age of 30, it tends to be more aggressive.
Increased spleen and/or liver associated with a very high white blood cell count is a typical CML finding.
The CML is divided into 3 phases:
Chronic phase: it is the phase in which 85% of the patients are diagnosed. The disease is milder and easily controlled with medications. This phase can last several years.
Accelerated phase: This is the phase where blasts begin to occur. The patient no longer responds so well to treatment.
Blast phase: It is the transformation of CML into AML, but in this case the response to treatment is very frustrating. The mean survival at this stage is only 6 months.
Treatment of CML
The goal of treatment is to eliminate all cells that have the Philadelphia chromosome, trying to prevent the evolution of the chronic disease to the accelerated and blastic phases. There is a new class of drugs that works to eliminate these defective cells. The drug most commonly used for this purpose is Imatinib (Gleevec).
The response is very good, above 75%, however, its use is indefinite, since the interruption of the drug is associated with recurrence of neoplastic cells.
Bone marrow transplantation is the only treatment that leads to healing and is the best option for those who do not have a good response to Imatinib. The major problem is the high rate of complications associated with the procedure.
The ALL is characterized by a large production of immature lymphocytes, called lymphoblasts. It is the most common leukemia in children, and is also quite common in adults. The prognosis of the disease in children is currently much better than in adults.
Fever, with or without an apparent cause, is one of the most common symptoms of ALL. As with any leukemia, the definitive diagnosis of ALL is made through bone marrow biopsy.
Treatment of ALL
The treatment of acute lymphocytic leukemia is divided into 3 parts.
Induction phase: the goal is to eliminate all neoplastic cells from the circulation. The treatment is done with chemotherapy + corticosteroids for 4 weeks.
Consolidation phase: the consolidation phase aims to prevent the return of cancer cells after induction. This phase can be done by repeating the induction schedule with smaller doses or with bone marrow transplantation.
Maintenance phase: chemotherapy treatment is usually extended for another 2 years. The goal is to eliminate any residual leukemia that may still exist without being detected in the exams.
While in children this protocol reaches cure rates above 80%, in adults the results are much less expressive, with success in only 20-30%. Children over 10 years of age present a worse response than younger children. B lymphocyte leukemias have a better prognosis than T lymphocyte leukemia.
CLL is mature lymphocyte leukemia. It is the most common form of leukemia in adults, except in Asian countries. It is a disease of older adults, mainly affecting those over 55 years.
As with CML, CLL is slower than its acute form. Survival usually ranges from 2 to 10 years.
The picture is usually insidious. Lymph node enlargement (ganglia), localized or generalized, is the most common sign, occurring in up to 90% of patients. Spleen enlargement is also common.
There are 2 clinical assessment systems that aim to classify patients according to the severity of CLL.
The Rai system is divided from 0 to 4, while the Binet system is divided into A, B and C. Both take into account the degree of distribution of lymph nodes, enlargement of the spleen and liver, and the presence of anemia and drop in platelets.
Treatment of LLC
Patients with CLL Binet A or Rai 0, 1 or 2, in general, present a good prognosis and slow evolution, and no treatment with chemo is indicated. Treatment is only indicated if there is progression of the disease. Those with more aggressive disease are treated with chemotherapy + synthetic antibodies against lymphocytes (Alemtuzumab or Rituximab).
Bone marrow transplantation is the only curative treatment, but its complication rate is very high, especially in the elderly.
